Using surface plasmon resonance spectroscopy to characterize the inhibition of NGF-p75(NTR) and proNGF-p75(NTR) interactions by small molecule inhibitors.

Abstract

Nerve growth factor (NGF), a member of the neurotrophin family, acts to influence the survival and differentiation of neurons in both the central and peripheral nervous systems via its binding to the p75(NTR) and TrkA receptors. Its precursor, proNGF, has been shown to be the dominant form of NGF in the central nervous system, suggesting a biological function beyond its role as a precursor. Like NGF, proNGF is known to bind the p75(NTR) receptor. The dysregulation of both NGF and proNGF have been implicated in several pathologies, including neurodegenerative diseases linked to p75(NTR)-mediated apoptotic signaling. Therefore, the identification of small molecule inhibitors capable of inhibiting both NGF and proNGF-p75(NTR) interactions may be of therapeutic interest. In the present study, we examine the inhibitory action of known small molecule-based inhibitors PD90780, ALE-0540, Ro 08-2750, and PQC 083, as well as novel derivatives of these compounds, using surface plasmon resonance (SPR) spectroscopy.